Endocrine abnormalities occur either as ?self-defined? disorders or in combination with other diseases. An ever-increasing number of ?non-endocrine? diseases also are found to be associated with endocrine abnormalities. Optimal use of valid laboratory tests and correct diagnosis of endocrine diseases or the endocrine components of ?non-endocrine? diseases obviously are important both medically and economically. Thyroid diseases represent the most common endocrine abnormalities, while other endocrine diseases such as pheochromocytoma are relatively uncommon. Although pheochromocytoma is a rare cause of hypertension, case findings require screening of a large numbers of patients. Nearly one in four Americans has hypertension, but only 0.1-0.5% of these patients will be found to have pheochromocytoma. Nevertheless, diagnosing these patients is important since ~90% can be cured with surgery, while the consequences can be catastrophic for the patient if the disease goes unrecognized and/or untreated. Over the past year, we evaluated a recently developed commercial HPLC method for plasma free metanephrines against our clinically validated HPLC method with respect to both analytical performance in general and diagnostic performance for pheochromocytoma in particular. There were good correlations between the two methods for both free metanephrine (r2 = 0.81) and free normetanephrine (r2 = 1.00). Linearity, imprecision assessed with within-run and between-run coefficients of variation, and recovery of added analytes were all similar with the two methods for both free metanephrines and normetanephrines. Unlike our in-house method, the commercial method did not suffer from interference with acetaminophen. Since the performance of the two methods for diagnosing pheochromocytoma was also similar in various groups of the study subjects (patients with confirmed diagnosis of pheochromocytoma, patients in whom pheochromocytoma was not confirmed, and apparently healthy adults volunteers), the commercial method was considered satisfactory for routine laboratory use. Validation of this commercial method for free metanephrines allows for wider availability of a technology that was previously limited to a few laboratories and this, in turn, is expected to improve the diagnosis of patients with pheochromocytoma nationwide. In addition to being reliable, the new commercial method also is cost-effective for diagnosing pheochromocytoma.